FLUCONAZOLE RESISTANCE IN OROPHARYNGEAL CANDIDIASIS

氟康唑是非常有效的治疗口腔鹅口疮， 复发性口咽念珠菌病患者数量增加 已经开发出氟康唑耐药酵母菌， 氟康唑治疗 氟康唑耐药性可以在一个单一的 持久性酵母菌株，但更常见的是氟康唑耐药 不同的白色念珠菌菌株或另一种菌株的出现 念珠菌属。较高剂量的氟康唑对抗真菌更有效 耐药菌株在小鼠念珠菌病，但效用鉴定 耐药菌株和用高剂量的 氟康唑未确立。 因此，本提案的目标是 前瞻性地确定氟康唑耐药的流行病学 口咽念珠菌病，将治疗反应与 氟康唑耐药，并评估更高剂量的 氟康唑治疗耐药酵母菌。 这些目标将 通过纵向评估HIV感染/AIDS患者实现 用氟康唑治疗复发性口咽念珠菌病。 的 这些研究的目的是改善口咽疾病的治疗， HIV感染/AIDS患者中的念珠菌病。 的具体目标 这一建议是：1）纵向评估一组患者， 复发性口咽念珠菌病与氟康唑的开发 耐药性并将耐药性与临床反应联系起来 治疗; 2）使用分子表征建立菌株身份 为了建立氟康唑的流行病学， 耐药口咽念珠菌病; 3）相关的抗真菌 药敏试验与临床结果，并确定效用 药敏技术检测氟康唑耐药 评价高剂量氟康唑对耐药酵母菌的作用 在念珠菌病的小鼠模型中; 5）为了确定 大剂量氟康唑治疗氟康唑耐药患者 酵母

Fluconazole is very effective in the treatment of oral thrush, but an increasing number of patients with recurrent oropharyngeal candidiasis have developed fluconazole-resistant yeasts following repeated courses of fluconazole therapy. Fluconazole resistance can develop in a single persistent strain of yeast, but more commonly fluconazole resistance results from emergence of a different Candida albicans strain or another Candida species. Higher doses of fluconazole are more effective against resistant strains in murine candidiasis, but the utility of identifying resistant isolates and treating resistant yeasts with high doses of fluconazole is not established. Thus, the objectives of this proposal are to define prospectively the epidemiology of fluconazole-resistant oropharyngeal candidiasis, to correlate therapeutic response with fluconazole resistance, and to evaluate the role of higher doses of fluconazole in treating resistant yeasts. These objectives will be achieved by longitudinally evaluating patients with HIV infection/AIDS treated with fluconazole for recurrent oropharyngeal candidiasis. The goal of these studies is to improve the treatment of oropharyngeal candidiasis in patients with HIV infection/AIDS. The specific aims of this proposal are: 1) To longitudinally evaluate a cohort of patients with recurrent oropharyngeal candidiasis for the development of fluconazole resistance and to correlate that resistance with clinical response to therapy; 2) To establish strain identity using molecular characterization of the yeasts in order to establish the epidemiology of fluconazole- resistant oropharyngeal candidiasis; 3) To correlate antifungal susceptibility testing with clinical outcome and to determine the utility of screening susceptibility techniques to detect fluconazole resistant yeasts; 4) To evaluate high doses of fluconazole against resistant yeasts in a murine model of candidiasis; 5) To determine the clinical utility of high doses of fluconazole in treating patients with fluconazole-resistant yeasts.